This proposal is in response to the announcement in the NIH Guide from the Pharmacology-Toxicology Program of the National Institute of General Medical Sciences for pharmacologic studies in Infants and Children. The proposed research has two areas of emphasis on antibiotic pharmacology in infants and children. The pharmacokinetic characteristics of chloramphenicol sodium succinate, following intravenous administration to newborns, infants and children will be determined with an enzymatic micro-assay. From the pharmacokinetic data, programs which detail dose, frequency and duration of administration which maintain blood concentrations between 5 and 25 micrograms/ml, can be developed for infants between one day and six years of age. Efficacy and toxicity of an increased dosage of gentamicin in immunosuppressed children will be examined. Classic methods of purification will be used to isolate R-factor mediated enzymes which inactivate semi-synthetic aminoglycosides, cephalosporins and spectinomycin. These enzymes will serve as reagents in the development of micro-assays. The assays will be developed to have the broadest applicability (ie feasible for many labs) and used to describe pharmacokinetic characteristics of the respective drugs in infants and children.